Patients with primary breast cancer MedDRA version: 20.0 Level: LLT Classification code 10006188 Term: Breast cancer female NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Abraxane
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
GBG Forschungs GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be eligible for study participation only if they comply with the following criteria: •Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures. •Complete baseline documentation must be sent to GBG Forschungs GmbH. •Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint. •Tumor lesion in the breast with a palpable size of = 2 cm or a sonographical size of = 1 cm in maximum diameter. The lesion has to be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion. •Patients must be in the following stages of disease: - cT2 - cT4a-d or - cT1c and cN+ or - cT1c and pNSLN+ or - cT1c and ER-neg and PR-neg or - cT1c and Ki67>20% - cT1c and HER2-pos •In patients with multifocal or multicentric breast cancer, the largest lesion should be measured. •Centrally confirmed ER/PR/HER-2, Ki-67 and SPARC status detected on core biopsy. ER/PR positive is defined as >1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridisation (ISH) ratio >2.2. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization. •Age = 18 years. •Karnofsky Performance status index = 80%. •Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results must be above the normal limit of the institution. For patients with HER2-positive tumors LVEF must be above 55%. •Laboratory requirements: Hematology - Absolute neutrophil count (ANC) = 2.0 x 109 / L and - Platelets = 100 x 109 / L and - Hemoglobin = 10 g/dL (= 6.2 mmol/L) Hepatic function - Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 1200
Exclusion criteria
Exclusion criteria: •Prior chemotherapy for any malignancy. •Prior radiation therapy for breast cancer. •Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment. •Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy). •Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer). •Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >160 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease. •History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent •Pre-existing motor or sensory neuropathy of grade 2 or more by NCI-CTC criteria v 4.0. •Currently active infection. •Definite contraindications for the use of corticosteroids. •Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol. •Concurrent treatment with: - chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (10 mg or less methylprednisolone or equivalent). - sex hormones. Prior treatment must be stopped before study entry. - other experimental drugs or any other anti-cancer therapy. •Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry. •Male patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer.;Secondary Objective: •To assess the pCR rates per arm separately for the stratified subpopulations. •To determine the rates of ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0; and regression grades. •To determine the response rates of the breast tumor and axillary nodes for both arms. •To assess clinical response rate after taxane in both groups •To determine the breast conservation rate after each treatment. •To assess the time of onset of grade 3 neuropathy •To assess the time of resolution of grade 3/4 neuropathy to at least grade 1 •To assess quality of life with a focus on persisting peripheral neuropathy using the FACT Taxane (Version 4) questionnaire, treatment of PNP, and cardiac toxicity. •To determine loco-regional invasive recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS) in both arms and according to stratified subpopulations. •To identify early relapses based on ctDNA during Follow up.;Primary end point(s): Primary efficacy endpoint: Pathological complete response of breast and lymph nodes (ypT0 ypN0; primary endpoint) ;Timepoint(s) of evaluation of this end point: Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Secondary short-time efficacy endpoints (ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0, and regression grade, response by physical examination, imaging response, breast conservation) 2. Loco-regional invasive recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS) 3. Tolerability and Safety: Descriptive statistics for the 4 treatments (each taxane +/- anti-HER2-treatment) will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped. 4. Translational research: Exploratory analyses will be performed to identify possible relationships between biomarkers and drug activity.;Timepoint(s) of evaluation of this end point: 1. Clinical (c) and imaging (i) response will be assessed every 2nd cycle and before surgery by physical examination and imaging tests. 2. LRRFS, RRFS, LRFS, DDFS, IDFS and OS are defined as the time period between registration and first event. 3. Throughout the 24 weeks treatment period and the 30 day safety follow up 4. With core examination and surgery. In addition and optional after 4th cycle, before and after surgery. | — |
Countries
Germany
Outcome results
None listed